A human IgM enriched immunoglobulin preparation, Pentaglobin, reverses autoimmune diabetes without immune suppression in NOD mice

Wilson, Christopher; Hoopes, Emilee M; Falk, Alexander; Moore, Daniel J.

doi:10.1038/s41598-022-15676-8

Cited by 5 publications

(5 citation statements)

References 25 publications

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“…The intraperitoneal injection of purified IgM isolated from Swiss Webster mice into VH125 SD .NOD mice resulted in a complete loss of detectable insulin-binding B cells in the spleen [ 155 ]. A similar strategy currently being studied in NOD mice is Pentaglobin treatment, a human immunoglobulin preparation enriched in IgM, which led to the expansion of thymic B cells and regulatory T cells (Tregs) and short-term reversal of T1D in ~78% of mice enrolled in the study [ 163 ]. Translation of these antigen-specific therapies from mouse to human may support the development of successful non-immunosuppressive T1D treatments in the future.…”

Section: Antigen-specific Therapy In T1dmentioning

confidence: 99%

Factors Governing B Cell Recognition of Autoantigen and Function in Type 1 Diabetes

Bass,

Bonami

2024

Antibodies

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Islet autoantibodies predict type 1 diabetes (T1D) but can be transient in murine and human T1D and are not thought to be directly pathogenic. Rather, these autoantibodies signal B cell activity as antigen-presenting cells (APCs) that present islet autoantigen to diabetogenic T cells to promote T1D pathogenesis. Disrupting B cell APC function prevents T1D in mouse models and has shown promise in clinical trials. Autoantigen-specific B cells thus hold potential as sophisticated T1D biomarkers and therapeutic targets. B cell receptor (BCR) somatic hypermutation is a mechanism by which B cells increase affinity for islet autoantigen. High-affinity B and T cell responses are selected in protective immune responses, but immune tolerance mechanisms are known to censor highly autoreactive clones in autoimmunity, including T1D. Thus, different selection rules often apply to autoimmune disease settings (as opposed to protective host immunity), where different autoantigen affinity ceilings are tolerated based on variations in host genetics and environment. This review will explore what is currently known regarding B cell signaling, selection, and interaction with T cells to promote T1D pathogenesis.

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Section: Antigen-specific Therapy In T1dmentioning

confidence: 99%

Factors Governing B Cell Recognition of Autoantigen and Function in Type 1 Diabetes

Bass,

Bonami

2024

Antibodies

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“…IFN-γ, TNF-α, IL-6, IL-8, IL-1β, IL-10) ( 167 – 169 , 174 ). Furthermore, Pentaglobin demonstrated immunomodulatory effects on T-cells in vitro and in vivo ( 168 , 175 , 176 ).…”

Section: Iga As Therapeutic Antibodymentioning

confidence: 99%

A new hope? Possibilities of therapeutic IgA antibodies in the treatment of inflammatory lung diseases

Bohländer

2023

Front. Immunol.

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Inflammatory lung diseases represent a persistent burden for patients and the global healthcare system. The combination of high morbidity, (partially) high mortality and limited innovations in the last decades, have resulted in a great demand for new therapeutics. Are therapeutic IgA antibodies possibly a new hope in the treatment of inflammatory lung diseases? Current research increasingly unravels the elementary functions of IgA as protector against infections and as modulator of overwhelming inflammation. With a focus on IgA, this review describes the pathological alterations in mucosal immunity and how they contribute to chronic inflammation in the most common inflammatory lung diseases. The current knowledge of IgA functions in the circulation, and particularly in the respiratory mucosa, are summarized. The interplay between neutrophils and IgA seems to be key in control of inflammation. In addition, the hurdles and benefits of therapeutic IgA antibodies, as well as the currently known clinically used IgA preparations are described. The data highlighted here, together with upcoming research strategies aiming at circumventing the current pitfalls in IgA research may pave the way for this promising antibody class in the application of inflammatory lung diseases.

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“…The Fc region can also be modified to alter pharmacokinetic properties and effector functions. On the other hand, although not subjected to Fc engineering, depending on the antigen or donor population, specific antiviral polyclonal IGs can be "enriched" for a particular isotype 18 , subclass, or glycosylation signature, leading to different Fc effector functions compared to other polyclonal IG products. For example, IgG1 and IgG4 are the most prevalent subclasses following measles infection or vaccination, with significant differences in titers in infected versus vaccinated individuals 19 .…”

Section: Antibodies As Therapeuticsmentioning

confidence: 99%

Uses and Challenges of Antiviral Polyclonal and Monoclonal Antibody Therapies

Struble¹,

Rawson²,

Stantchev³

et al. 2023

Preprint

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Viral diseases represent a major public health concern and an ever-present risk for developing into a future pandemic. Antiviral antibody therapeutics, either alone or in combination with other therapies, have emerged as valuable preventative and treatment options, including during a global emergency. Here we will discuss polyclonal and monoclonal antiviral antibody therapies, focusing on the unique biochemical and physiological properties that make them well suited as therapeutic agents. We will describe the methods of antibody characterization and potency assessment throughout development, highlighting similarities and differences between polyclonal and monoclonal products as appropriate. In addition, we will consider the benefits and challenges of antiviral antibodies when used in combination with other antibodies or other types of antiviral therapeutics. Lastly, we will discuss novel approaches to the characterization and development of antiviral antibodies and identify areas that would benefit from additional research.

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A human IgM enriched immunoglobulin preparation, Pentaglobin, reverses autoimmune diabetes without immune suppression in NOD mice

Cited by 5 publications

References 25 publications

Factors Governing B Cell Recognition of Autoantigen and Function in Type 1 Diabetes

Factors Governing B Cell Recognition of Autoantigen and Function in Type 1 Diabetes

A new hope? Possibilities of therapeutic IgA antibodies in the treatment of inflammatory lung diseases

Uses and Challenges of Antiviral Polyclonal and Monoclonal Antibody Therapies

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